Genetic causes of diabetes mellitus type 2
Most cases of diabetes mellitus type 2 involved many genes contributing small amount to the overall condition. As of 2011 more than 36 genes have been found that contribute to the risk of type 2 diabetes. All of these genes together still only account for 10% of the total genetic component of the disease.
There are a number of rare cases of diabetes that arise due to an abnormality in a single gene (known as monogenic forms of diabetes). These include maturity onset diabetes of the young (MODY), Donohue syndrome, and Rabson-Mendenhall syndrome, among others. Maturity onset diabetes of the young constitute 1–5% of all cases of diabetes in young people.
Genes associated with developing type 2 diabetes, include TCF7L2, PPARG, FTO, KCNJ11,NOTCH2, WFS1, IGF2BP2, SLC30A8, JAZF1, HHEX among others.KCNJ11 (potassium inwardly rectifying channel, subfamily J, member 11), encodes the islet ATP-sensitive potassium channel Kir6.2, and TCF7L2 (transcription factor 7–like 2) regulates proglucagon gene expression and thus the production of glucagon-like peptide-1. In addition, there is also a mutation to the Islet Amyloid Polypeptide gene that results in an earlier onset, more severe, form of diabetes.
Various hereditary conditions may feature diabetes, for example myotonic dystrophy and Friedreich's ataxia. Wolfram's syndrome is an autosomal recessive neurodegenerative disorder that first becomes evident in childhood. It consists of diabetes insipidus, diabetes mellitus, optic atrophy, and deafness, hence the acronym DIDMOAD.
While obesity is an independent risk factor for type 2 diabetes that may be linked to lifestyle, obesity is also a trait that may be strongly inherited. Other research also shows that type 2 diabetes can cause obesity as an effect of the changes in metabolism and other deranged cell behavior attendant on insulin resistance.
However, environmental factors (almost certainly diet and weight) play a large part in the development of type 2 diabetes in addition to any genetic component. Genetic risk for type 2 diabetes changes as humans first began migrating around the world, implying a strong environmental component has affected the genetic-basis of type 2 diabetes. This can be seen from the adoption of the type 2 diabetes epidemiological pattern in those who have moved to a different environment as compared to the same genetic pool who have not. Immigrants to Western developed countries, for instance, may be more prone to diabetes as compared to its lower incidence in their countries of origins. Such developments can also be found in environments which have had a recent increase in social wealth, increasingly common throughout Asia.
- Williams textbook of endocrinology. (12th ed. ed.). Philadelphia: Elsevier/Saunders. pp. 1371–1435. ISBN 978-1-4377-0324-5.
- Herder, C; Roden, M (Jun 2011). "Genetics of type 2 diabetes: pathophysiologic and clinical relevance.". European journal of clinical investigation 41 (6): 679–92. doi:10.1111/j.1365-2362.2010.02454.x. PMID 21198561.
- "Monogenic Forms of Diabetes: Neonatal Diabetes Mellitus and Maturity-onset Diabetes of the Young". National Diabetes Information Clearinghouse (NDIC) (National Institute of Diabetes and Digestive and Kidney Diseases, NIH). Retrieved 2008-08-04.
- Lyssenko V, Jonsson A, Almgren P, et al. (November 2008). "Clinical risk factors, DNA variants, and the development of type 2 diabetes". The New England Journal of Medicine 359 (21): 2220–32. doi:10.1056/NEJMoa0801869. PMID 19020324.
- McCarthy, M. I. (December 2010). Feero, W. G.; Guttmacher, A. E., eds. "Genomics, Type 2 Diabetes, and Obesity". The New England Journal of Medicine 363 (24): 2339–50. doi:10.1056/NEJMra0906948. PMID 21142536.
- Rother KI (April 2007). "Diabetes treatment—bridging the divide". The New England Journal of Medicine 356 (15): 1499–501. doi:10.1056/NEJMp078030. PMID 17429082.
- Sakagashira S, Sanke T, Hanabusa T, et al. (September 1996). "Missense mutation of amylin gene (S20G) in Japanese NIDDM patients". Diabetes 45 (9): 1279–81. doi:10.2337/diabetes.45.9.1279. PMID 8772735.
- Cho YM, Kim M, Park KS, Kim SY, Lee HK (May 2003). "S20G mutation of the amylin gene is associated with a lower body mass index in Korean type 2 diabetic patients". Diabetes Res. Clin. Pract. 60 (2): 125–9. doi:10.1016/S0168-8227(03)00019-6. PMID 12706321. Retrieved 19 July 2008.
- Barrett TG (September 2001). "Mitochondrial diabetes, DIDMOAD and other inherited diabetes syndromes". Best Practice & Research. Clinical Endocrinology & Metabolism 15 (3): 325–43. doi:10.1053/beem.2001.0149. PMID 11554774.
- Walley AJ, Blakemore AI, Froguel P (October 2006). "Genetics of obesity and the prediction of risk for health". Human Molecular Genetics. 15 Spec No 2: R124–30. doi:10.1093/hmg/ddl215. PMID 16987875.
- Camastra S, Bonora E, Del Prato S, Rett K, Weck M, Ferrannini E (December 1999). "Effect of obesity and insulin resistance on resting and glucose-induced thermogenesis in man. EGIR (European Group for the Study of Insulin Resistance)". Int. J. Obes. Relat. Metab. Disord. 23 (12): 1307–13. doi:10.1038/sj.ijo.0801072. PMID 10643689.
- Corona, Erik. "Geneworld". World Wide Patterns of Genetic Risk for Disease. Stanford University. Retrieved 11 September 2013.
- Gibbons, Ann (4 November 2011). "Diabetes Genes Decline Out of Africa". Science 334 (6056): 583. doi:10.1126/science.334.6056.583.
- Cotran, Kumar, Collins; Robbins Pathologic Basis of Disease,Saunders Sixth Edition, 1999; 913-926.